The impact of bioactive lipids on cardiovascular development

Abstract

Lysophospholipids comprise a group of bioactive molecules with multiple biological functions. The cardinal members of this signalling molecule group are sphingosylphosphorylcholine (SPC), lysophosphatidic acid (LPA), and sphingosine 1-phosphate (S1P) which are, at least in part, homologous to each other. Bioactive lipids usually act via G-protein coupled receptors (GPCRs), but can also function as direct intracellular messengers. Recently, it became evident that bioactive lipids play a role during cellular differentiation development. SPC induces mesodermal differentiation of mouse ES cells and differentiation of promyelocytic leukemia cells, by a mechanism being critically dependent on MEK-ERK signalling. LPA stimulates the clonal expansion of neurospheres from neural stem/progenitor cells and induces c-fos via activation of mitogen- and stress-activated protein kinase 1 (MSK1) in ES cells. S1P acts on hematopoietic progenitor cells as a chemotactic factor and has also been found to be critical for cardiac and skeletal muscle regeneration. Furthermore, S1P promotes cardiogenesis and similarly activates Erk signalling in mouse ES cells. Interestingly, S1P may also act to maintain human stem cell pluripotency. Both LPA and S1P positively regulate the proliferative capacity of murine ES cells. In this paper we will focus on the differential and developmental impact of lysophospholipids on cardiovascular development.

Figure 1

Lysophospholipid receptor expression in murine pluripotent stem cells. Heatmap of microarray gene expression of a list of mouse bioactive lipid receptors. Gene expression color key is shown in log2 scale. Microarray data were downloaded from the GEO database; accession numbers GSE10806.

Figure 2

Lysophospholipid receptor expression in human pluripotent stem cells. Heatmap of microarray gene expression of a list of human bioactive lipid receptors. Gene expression color key is shown in log2 scale. Microarray data were downloaded from the GEO database; accession numbers GSE151716.

Figure 3

Schematic illustration of SPC-induced differentiation in murine multipotent and pluripotent stem cells. Signaling pathways mediating the respected phenotype are noted next to black arrows.

Figure 4

In vivo model of S1P function and its respective cofactors in the developing zebrafish.